# Anatomy of the circle of Willis, cerebral blood flow, and Alzheimer's disease biomarkers in hypertension

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $823,478

## Abstract

SUMMARY
 Hypertension (HTN), affects over 60% of US population above 60. It increases the risk of Alzheimer's disease
(AD) through compromised regulation of cerebral blood flow (CBF). Multiple studies failed to establish that
lowering blood pressure (BP) entails consistent benefits for cognition and brain measures. This is probably due
to a preexisting compromise of the vascular system, which does not compensate properly for relative perfusion
pressure decrease caused by BP lowering. In a previous cycle, we showed that, in HTN, there is an optimal BP
level that maximizes CBF. We also show 1) an optimal BP that decreases white matter lesion risk, 2) perfusion
correlates with tau pathology, and 3) all these findings occur in older HTN subjects. Despite these new
discoveries, there is a large variance in CBF and cognition due factors other than age and BP, suggesting the
need for further fine-tuning of the model for optimal BP. In this competitive renewal of our NIH/NHLBI R01
HL111724 we propose to focus on variants of the circle of Willis (CoW). They adversely influence CBF and
outcome in chronic and acute conditions. However, very little is known about how they affect perfusion, cognition
and AD markers in HTN. Our data indicate that incomplete variants play a role in circumstances when there is
already a pre-existing impairment of the vascular system (HTN). We offer that these variants in the setting of
HTN necessitate higher perfusion pressure to maintain adequate blood flow, thus increasing the risk for
hypoperfusion and AD-related pathology.
 Over a 2-year we will enroll 140 hypertensive, cognitively healthy subjects, 70-85 years old, with (n=70) and
without (n=70) typical anatomy of the CoW. At baseline and 24-month follow-up, we will perform BP and cognition
assessments, magnetic resonance imaging (including perfusion and vessel anatomy). 50% of the group will
receive both tau (PI-2620) and amyloid (Neuraceq) positron emission tomography at baseline and follow-up. We
will test whether: AIM1. H1. For the same BP, CBF is lower in subjects with an incomplete CoW than in subjects
with a complete circle. H2. Longitudinally, in subjects with an incomplete CoW, for the same baseline BP, an
equal reduction in BP entails greater reduction in CBF than in subjects with a complete circle. AIM2. H1. For the
same BP, baseline amyloid and tau accumulation is higher in subjects with an incomplete CoW than in subjects
with a complete circle. H2. AD biomarkers correlate with CBF. H3. Longitudinally, in subjects with an incomplete
CoW, for the same baseline BP, an equal reduction in BP entails greater accumulation of amyloid and tau than
in subjects who have a complete circle. Secondary AIM. H1. Variants of the posterior circulation (incomplete
posterior circle, vertebral artery hypoplasia) are selectively related to lower hippocampal CBF, and to H2. higher
hippocampal tau accumulation.
We hope our research will contribute to fine-tuning of HTN management and ...

## Key facts

- **NIH application ID:** 10367312
- **Project number:** 2R01HL111724-06A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Lidia Glodzik
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $823,478
- **Award type:** 2
- **Project period:** 2012-03-06 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367312

## Citation

> US National Institutes of Health, RePORTER application 10367312, Anatomy of the circle of Willis, cerebral blood flow, and Alzheimer's disease biomarkers in hypertension (2R01HL111724-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10367312. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*